The subject of the invention.is a method for accelerating the rate of digestion of a protein, and the use of a protein thus modified for preparing a food or pharmaceutical composition for modulating the postprandial plasmatic level of amino acids.
In humans, during a nycthemeron, food intake is discontinuous. Postprandial periods, i.e. the phases of nutrient assimilation from the digestive tract, alternate with periods of physiological fast. These diurnal variations in the nutritional status affect the components of protein metabolism, and consequently the protein balance.
Thus, the consumption of proteins results in an increase in the plasmatic level of amino acids (Aoki et al., Am. J. Olin. Nutr., 41, 1-18, 1987). Similarly, the elevation of the plasmatic level of amino acids is associated with a decline in proteolysis and a stimulation of the oxidation of amino acids and of protein synthesis (Castellino et al., Am. J. Physiol., 262, 162-176, 1992; Giordano et al., Diabetes, 45, 393-399, 1996; Clugston et al., Olin. Nutr., 36, 57-70, 1982; Motil et al., Am. J. Physiol., 240, E712-721, 1981; Melville et al., Metabolism., 30, 248-255, 1989; Pacy et al., Olin. Sci., 86, 103-118, 1994).
The protein balance, which is negative during the period of physiological fast, becomes positive during the postprandial period. The relative extent of each phase therefore determines the evolution of the protein mass of the body. It is thus essential to be able to magnify the postprandial protein gain in order to optimize the evolution of the protein mass in numerous circumstances.
Recently, Boirie et al. have shown, in healthy young volunteers, that the postprandial protein gain depends on the rate of digestion of the ingested proteins (delay between the ingestion and the absorption of the nutriments by the body), this phenomenon being linked to the structure of the proteins. Lactoserum administered in a single oral dose induces a very early appearance in the blood of amino acids of food origin, the effect of which is a peak of plasmatic concentration of amino acids. A clear stimulation of protein synthesis and of oxidation of leucine is also observed. These postprandial modifications lead to a considerable improvement in the protein gain with respect to the period of physiological fast (Boirie et al., Am. J. Physiol., 271, E1083-1091, 1996).
In comparison with lactoserum, the amino acids which are derived from casein are absorbed progressively over a longer period. In this case, the plasmatic concentration of amino acids rises moderately, but this rise persists with time, several hours after a meal (Boirie et al., Nutr. Olin. Metabol., 9, 171, 1995).
The rate of digestion is thus different between these two types of protein, lactoserum thus being classified among the rapidly digested proteins, and casein being classified among the slowly digested proteins.
The behavior of rapidly digested proteins can be exploited for the nutrition of subjects with a considerable and immediate physiological requirement for amino acids, to maintain their body mass, such as patients who have just had a surgical operation (Arnold et al., Nutr. Olin. Metabol., 6, 3-12, 1992); children (Dewey et al., Eur. J. Olin. Nutr., 50, supplement 1, S119-150, 1996); or sportspersons, in particular after a physical effort, for example (Biolo et al., Am. J. Physiol., 273, E122-129, 1997; Rennie et al., In Physical Activity, Fitness and Health: Physical Activity and Protein Metabolism, Bouchard et al., Champaign, Ill., Human kinetics, 432-450, 1994).
Rapidly digested proteins can also be exploited for the nutrition of subjects with nausea, vomiting, and/or a sensation of satiety that is too strong and protracted after a meal, such that they experience discomfort, or even difficulties, in eating regularly and/or sufficiently. The people concerned can be subject to passing nausea, such as pregnant women; or can have gastrointestinal motility disorders, in particular elderly people and people with a pathological state such as anorexia, diabetes, the presence of a gastric carcinoma, neurological disorders (e.g., Parkinson""s disease), drug or alcohol dependency, etc., for example (Maes et al., in 13CO2 Breath test at the laboratory: Digestion-Absorption, Y. Groos Ed., p.55-69, 1996).
Rapidly digested proteins can also be exploited for limiting the risks of regurgitation and/or gastro-esophageal reflux, in particular in infants, premature babies, pregnant women or patients fed by the enteral route (Fried et al., J. Pediatr., 120, 569-572, 1992).
To date, it has never been proposed to accelerate the rate of digestion of a protein, in particular in order to modulate the postprandial plasmatic level of amino acids, and as a result to modulate the postprandial protein gain, and/or to limit the postprandial sensations of nausea in pregnant women, and/or to limit the problems linked to gastrointestinal motility disorders and/or to limit the postprandial risks of regurgitation and of gastro-esophageal reflux.
In addition, some slowly digested proteins, such as casein, can have a high nutritive value, i.e. a balanced and high content of each of the amino acids which are essential for the body, such as lysine, tryptophan, leucine, isoleucine, valine, phenylalanine, methionine and threonine, for example. Unfortunately, the nutritive value of these proteins is not sufficiently exploited in people with a physiological requirement for rapidly digested proteins.
Certain treatments of proteins are already known for modifying their rate of digestion. For example, W097/05785 (Milupa GmbH) indicates that treating proteins, in particular milk casein, with transglutaminase makes it possible to slow their rate of digestion. Transglutaminase (EC2.3.2.13), also known as Factor XIIIa, y-glutamyltransferase or fibrinoligase, is known to modify proteins by catalyzing polymerization, deamidation, and amine-incorporation reactions (Nielsen, Food biotechnol., 9, 119-156, 1995).
Similarly, soluble dietary fibers are known to increase the viscosity of the gastrointestinal content, and thus the time for hydrolysis and absorption of sugars (Cameron-Smith et al., Br. J. Nutr., 71, 563-571, 1994). In the same way, U.S. Pat. No. 5,126,332 (Terumo Kabushiki Kaisha) advocates mixing casein with carrageenans or a guar gum so as to form a gel in the stomach, which will be slowly broken up in the intestine, to slow the absorption of sugars, and probably also of casein, and thus to prevent a rapid increase in glucose in the blood of diabetics.
Finally, another efficient means for accelerating the rate of digestion of proteins generally consists in carrying out an extensive hydrolysis, until hydrolysis residues are obtained which are less than 10,000 Daltons, for example. To this end, U.S. Pat. No. 5,039,532 describes a method in which whey is subjected to a partial enzymatic hydrolysis by means of proteolytic enzymes, it is subjected to a heat treatment to denature the minor proteins, thus rendering them accessible to a subsequent enzymatic degradation, it is cooled and is then subjected to a second hydrolysis and heat treatment again to inactivate the enzyme (see also EP 96202475.8; EP 629350; JP 3-18168; Beaufrere et al., Am. J. Physiology, 30, E907-E914, 1994).
The present invention is directed to assisting in satisfying the nutritive requirements of certain categories of people, with proteins which are initially slowly digested proteins, and which have been transformed into rapidly digested proteins.
The invention thus is directed to compositions and methods involving the digestion of protein matter. One aspect of the present invention relates to a method for accelerating the rate of digestion of a protein matter, in which the protein matter is treated with transglutaminase and mixed with anionic polysaccharides. Compositions of the treated protein matter also represent yet another aspect of the invention.
Other aspects of the present invention include methods of modulating postprandial protein gain in mammals, reducing problems linked to gastrointestinal motility disorders in mammals, limiting nausea in pregnant women, and limiting risk of regurgitation and/or gastro-esophageal reflux in mammals. These methods may all be accomplished by oral administration of a composition comprising rapidly digested protein matter, i.e., protein matter which, when ingested by rats weighing from 140 grams to 200 grams, leads to a disappearance of half the ingested nitrogen present in the digestive tract in less than 70 minutes. To achieve this, the protein matter is pretreated so as to transform slowly digested proteins that it contains into rapidly digested proteins which have at least substantially conserved the same initial molecular weight. These methods can advantageously incorporate protein matter, the digestion rate of which can be accelerated, as stated above, through treatment of the protein matter with transglutaminase and mixing with anionic polysaccharides.
The anionic polysaccharides used in any or all of these methods can be alginates, xanthan, gum arabic, pectins, kappa-carrageenans, iota-carrageenans, lambda-carrageenans, carboxymethylcellulose, sulfated dextrans, gellan gum, or mixtures thereof. Preferably, the protein matter used in any or all of these methods may include milk proteins.
Additionally, the protein matter included or initially contained in any or all of these methods can include slowly digested proteins, i.e., proteins which, when ingested by rats weighing from 140 grams to 200 grams, lead to a disappearance of half the ingested nitrogen present in the digestive tract in more than 80 minutes. In a preferred embodiment, the treatment of the protein matter with transglutaminase and the addition of anionic polysaccharides are such that the protein matter thus treated, when ingested by rats weighing from 140 grams to 200 grams, leads to a disappearance of half the ingested nitrogen present in the digestive tract in less than 70 minutes.
Another aspect of the present invention is directed to a food or pharmaceutical composition including anionic polysaccharides, protein matter treated with transglutaminase, or a combination thereof.